In vascular smooth muscle (VSM), mechanical responses to contractile agonists require calcium ions derived from one or both of two sources, Ca ions from the extracellular fluid and/or Ca ions that is bound intracellularly probably at the inner aspect of the plasma membrane. It is postulated that phosphoinositides are involved in the regulation of Ca ions mobilization from both of these pools, i.e., phosphatidylinositol (PI) in plasma membrane permeability, and polyphosphoinositides (poly PI) in Ca ions binding inside the plasma membrane. Furthermore, smooth muscle cells of vascular strips from hypertensive rats behave in vitro as if they are hyperpermeable to Ca ions. This hyperpermeability may involve altered phosphoinositide turnover. The objectives of this research are therefore: 1) to determine the relationships that exist between agonist-induced phosphoinositide turnover, calcium mobilization and tension development in smooth muscle; and 2) to determine whether or not membrane inositol phospholipids are involved in the cell membrane hyperpermeability to calcium which is seen in vascular smooth muscle of hypertensive animals. In these studies we will attempt to correlate PI and poly PI turnover with tension development in vitro in two types of smooth muscle, aorta and guinea pig ileum, each exhibiting different degrees of pharmacomechanical coupling. We will explore PI and poly PI breakdown in relation to 45Ca binding to and release from plasma membranes isolated from vascular smooth muscle. These studies of phosphoinositide and calcium metabolism will extend to VSM from spontaneously hypertensive rats and rats made hypertensive by injections of deoxycorticosterone. The results of this research may expose another link in the chain of reactions occurring between agonist-receptor interaction and final contractile response in vascular smooth muscle. They may also help to explain the phenomenon of hyperreactivity in hypertension.